Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001486 (Adenovirus)
3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NM23, a novel gene associated with low tumor metastatic potential, has been investigated in an experimental system in which metastasis is inhibited by the transfection of viral and cellular oncogenes. The experimental system utilizes transfection of the Adenovirus 2 Ela gene to inhibit metastasis: rat embryo fibroblasts (REF) transfected with c-Ha-ras were highly metastatic, while REF cotransfected with ras and Ela were virtually nonmetastatic. NM23 RNA levels were higher in three independently ras + Ela-cotransfected, low metastatic REF lines than in three independently ras-transfected, highly metastatic REF line. Differences in hybridizable NM23 RNA levels between the two groups of transfected cell lines ranged from 2- to 8-fold. In situ hybridization demonstrated that the relatively high NM23 RNA levels in low metastatic ras + Ela-cotransfected REF cells were not due to overexpression of the NM23 gene by a subpopulation of cells. Thus, the metastasis-inhibitory effect of the exogenously added Ela gene has been associated with increased activation of the cellular NM23 gene. This associated is particularly significant in light of the very few changes observed in translatable steady-state RNA levels between ras- and ras + Ela-transfected REF lines. The data identify NM23 as a candidate for a gene that suppresses the malignant state.
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PMID:Altered expression of NM23, a gene associated with low tumor metastatic potential, during adenovirus 2 Ela inhibition of experimental metastasis. 246 Feb 24

Cell fusion experiments have predicted the existence of cancer metastasis suppressor genes. The E1a gene of Adenovirus 2 has been demonstrated to suppress c-Ha-ras induction of experimental metastatic potential in rat embryo fibroblasts. Another approach to the identification of candidate metastasis suppressor genes has utilized differential or subtraction hybridizations to clone genes which are downregulated as cells become highly metastatic. To date, three such genes have been identified: nm23, WDNM1, and fibronectin. With regard to nm23, downregulation of nm23 RNA levels in high metastatic potential cells has been demonstrated in a wide variety of rodent metastasis systems, including K-1735 murine melanoma cell lines, nitrosomethylurea-induced rat mammary tumors, MMTV-induced mouse mammary tumors, and ras +/- E1a transfected rat embryo fibroblasts. Whether the expression of the nm23 gene, and other down-regulated genes in tumor metastasis, correlates with changes in metastatic potential, or actually has suppressive activity, will require transfection experiments.
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PMID:Search for metastasis suppressor genes. 253 85